EP0078191A2 - Kollagenhemmende Zusammensetzungen; Verfahren zu ihrer Herstellung und ihren Verwendungen - Google Patents
Kollagenhemmende Zusammensetzungen; Verfahren zu ihrer Herstellung und ihren Verwendungen Download PDFInfo
- Publication number
- EP0078191A2 EP0078191A2 EP82401887A EP82401887A EP0078191A2 EP 0078191 A2 EP0078191 A2 EP 0078191A2 EP 82401887 A EP82401887 A EP 82401887A EP 82401887 A EP82401887 A EP 82401887A EP 0078191 A2 EP0078191 A2 EP 0078191A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- proline
- cis
- collagen
- hydroxy
- synthesis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920001436 collagen Polymers 0.000 title claims abstract description 101
- 102000008186 Collagen Human genes 0.000 title claims abstract description 93
- 108010035532 Collagen Proteins 0.000 title claims abstract description 93
- 239000000203 mixture Substances 0.000 title claims abstract description 55
- 238000000034 method Methods 0.000 title claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 title abstract description 30
- 238000004519 manufacturing process Methods 0.000 title abstract description 12
- 230000008569 process Effects 0.000 title abstract description 6
- 231100000241 scar Toxicity 0.000 claims abstract description 16
- 230000009772 tissue formation Effects 0.000 claims abstract description 5
- 150000003147 proline derivatives Chemical class 0.000 claims description 45
- PMMYEEVYMWASQN-IMJSIDKUSA-N cis-4-Hydroxy-L-proline Chemical compound O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 claims description 37
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 34
- 230000015572 biosynthetic process Effects 0.000 claims description 30
- 238000003786 synthesis reaction Methods 0.000 claims description 21
- 239000000835 fiber Substances 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 15
- 229920000642 polymer Polymers 0.000 claims description 14
- 229940081066 picolinic acid Drugs 0.000 claims description 10
- 229920001184 polypeptide Polymers 0.000 claims description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 10
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 5
- IADUEWIQBXOCDZ-UHFFFAOYSA-N (2S)-azetidine-2-carboxylic acid Natural products OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 claims description 4
- OMGHIGVFLOPEHJ-BYPYZUCNSA-N (2s)-2,5-dihydro-1h-pyrrole-2-carboxylic acid Chemical compound OC(=O)[C@H]1NCC=C1 OMGHIGVFLOPEHJ-BYPYZUCNSA-N 0.000 claims description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 4
- 150000005690 diesters Chemical class 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 3
- 230000006790 cellular biosynthetic process Effects 0.000 claims description 3
- 229910004727 OSO3H Inorganic materials 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 abstract description 17
- 210000004027 cell Anatomy 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 229960002429 proline Drugs 0.000 description 17
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 16
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000008021 deposition Effects 0.000 description 7
- 229940093499 ethyl acetate Drugs 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 206010052428 Wound Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229920000728 polyester Polymers 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
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- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000035508 accumulation Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229960003767 alanine Drugs 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000036573 scar formation Effects 0.000 description 3
- 210000001626 skin fibroblast Anatomy 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 210000002435 tendon Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- ZIWHMENIDGOELV-IMJSIDKUSA-N (2s,4s)-4-fluoropyrrolidin-1-ium-2-carboxylate Chemical compound OC(=O)[C@@H]1C[C@H](F)CN1 ZIWHMENIDGOELV-IMJSIDKUSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000032544 Cicatrix Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 208000002847 Surgical Wound Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
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- 230000037311 normal skin Effects 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
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- COMUWNFVTWKSDT-ZETCQYMHSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)ON1C(=O)CCC1=O COMUWNFVTWKSDT-ZETCQYMHSA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- 240000001606 Adenanthera pavonina Species 0.000 description 1
- 235000011470 Adenanthera pavonina Nutrition 0.000 description 1
- JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 244000068485 Convallaria majalis Species 0.000 description 1
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- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical class ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 101710137510 Saimiri transformation-associated protein Proteins 0.000 description 1
- 240000000513 Santalum album Species 0.000 description 1
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- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003413 degradative effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 238000002683 hand surgery Methods 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- -1 proline analogs Chemical class 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 125000003508 trans-4-hydroxy-L-proline group Chemical group 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- Yet another object of the present invention is to provide certain collagen-inhibiting compositions and methods to be used in treating animals to control and limit scar tissue formation due to wounds from trauma, including burns or diseases, after surgery, for the treatment of those diseases involving fibrosis, with excessive accumulations of collagen, such as pulmonary fibrosis, etc.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pyrrole Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT82401887T ATE21823T1 (de) | 1981-10-16 | 1982-10-14 | Kollagenhemmende zusammensetzungen; verfahren zu ihrer herstellung und ihren verwendungen. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/311,920 US4428939A (en) | 1981-10-16 | 1981-10-16 | Collagen inhibiting compositions and processes for manufacturing and using same |
| US311920 | 1981-10-16 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0078191A2 true EP0078191A2 (de) | 1983-05-04 |
| EP0078191A3 EP0078191A3 (en) | 1983-08-17 |
| EP0078191B1 EP0078191B1 (de) | 1986-09-03 |
Family
ID=23209071
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP82401887A Expired EP0078191B1 (de) | 1981-10-16 | 1982-10-14 | Kollagenhemmende Zusammensetzungen; Verfahren zu ihrer Herstellung und ihren Verwendungen |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4428939A (de) |
| EP (1) | EP0078191B1 (de) |
| JP (1) | JPS58140022A (de) |
| AT (1) | ATE21823T1 (de) |
| CA (1) | CA1239393A (de) |
| DE (2) | DE78191T1 (de) |
| IL (1) | IL67027A (de) |
| ZA (1) | ZA827359B (de) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995019764A1 (en) * | 1994-01-21 | 1995-07-27 | Jonathan Javitt | Cis-hydroxyproline analogs for eye treatment |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4625016A (en) * | 1981-10-16 | 1986-11-25 | University Of Medicine And Dentistry Of New Jersey | Collagen inhibiting compositions and processes for manufacturing and using same |
| US5372807A (en) * | 1990-05-14 | 1994-12-13 | University Of Medicine And Dentistry Of New Jersey | Polymers containing antifibrotic agents, compositions containing such polymers, and methods of preparation and use |
| US6517824B1 (en) | 1990-05-14 | 2003-02-11 | University Of Medicine & Denistry Of New Jersey | Polymer compositions comprising antifibrotic agents, and methods of treatment, pharmaceutical compositions, and methods of preparation therefor |
| US20030186869A1 (en) * | 1990-05-14 | 2003-10-02 | George Poiani | Polymer compositions comprising antifibrotic agents, and methods of treatment, pharmaceutical compositions, and methods of preparation therefor |
| US5660822A (en) * | 1990-05-14 | 1997-08-26 | University Of Medicine & Dentistry Of N.J. | Polymers containing antifibrotic agents, compositions containing such polymers, and methods of preparation and use |
| US5605938A (en) * | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate |
| US5705178A (en) * | 1991-05-31 | 1998-01-06 | Gliatech, Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
| JPH05202177A (ja) * | 1991-09-06 | 1993-08-10 | Teijin Ltd | 生分解性共重合体、及びそれを含有する医薬品組成物 |
| JP2552155Y2 (ja) * | 1992-01-07 | 1997-10-27 | パロマ工業株式会社 | 水量調節装置 |
| WO1993018760A1 (en) * | 1992-03-23 | 1993-09-30 | University Of Manitoba | Use of transglutaminase inhibitor for the treatment of scar tissue |
| DE10120456A1 (de) * | 2001-04-26 | 2002-11-14 | Degussa | Polymergebundener Katalysator für die enantioselektive Aldol-/Mannichreaktion |
| US20080057491A1 (en) * | 2003-02-07 | 2008-03-06 | Mckee Patrick A | Substrates and inhibitors of antiplasmin cleaving enzyme and methods of use |
| US8933201B2 (en) | 2006-06-07 | 2015-01-13 | The Board Of Regents Of The University Of Oklahoma | Substrates and inhibitors of antiplasmin cleaving enzyme and fibroblast activation protein and methods of use |
| BR112012028078B1 (pt) * | 2010-05-05 | 2021-03-30 | Basell Poliolefine Italia S.R.L. | Composições de polímero de propileno |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2228187A1 (de) * | 1971-06-10 | 1972-12-14 | Prockop, Darwin Johnson, Phila delphia, Pa (V St A ) | Arzneimittel |
| US3951939A (en) * | 1972-01-08 | 1976-04-20 | Behringwerke Aktiengesellschaft | Polypeptides, process for their manufacture and their use as polyvalent isoinhibitors |
| US4265805A (en) * | 1980-04-01 | 1981-05-05 | American Cyanamid Company | Polymeric light stabilizers containing tetralkyl piperidine moieties |
-
1981
- 1981-10-16 US US06/311,920 patent/US4428939A/en not_active Expired - Fee Related
-
1982
- 1982-10-07 ZA ZA827359A patent/ZA827359B/xx unknown
- 1982-10-14 JP JP57179194A patent/JPS58140022A/ja active Granted
- 1982-10-14 DE DE198282401887T patent/DE78191T1/de active Pending
- 1982-10-14 AT AT82401887T patent/ATE21823T1/de not_active IP Right Cessation
- 1982-10-14 DE DE8282401887T patent/DE3273044D1/de not_active Expired
- 1982-10-14 EP EP82401887A patent/EP0078191B1/de not_active Expired
- 1982-10-15 CA CA000413590A patent/CA1239393A/en not_active Expired
- 1982-10-20 IL IL67027A patent/IL67027A/xx unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2228187A1 (de) * | 1971-06-10 | 1972-12-14 | Prockop, Darwin Johnson, Phila delphia, Pa (V St A ) | Arzneimittel |
| US3951939A (en) * | 1972-01-08 | 1976-04-20 | Behringwerke Aktiengesellschaft | Polypeptides, process for their manufacture and their use as polyvalent isoinhibitors |
| US4265805A (en) * | 1980-04-01 | 1981-05-05 | American Cyanamid Company | Polymeric light stabilizers containing tetralkyl piperidine moieties |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995019764A1 (en) * | 1994-01-21 | 1995-07-27 | Jonathan Javitt | Cis-hydroxyproline analogs for eye treatment |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3273044D1 (en) | 1986-10-09 |
| IL67027A0 (en) | 1983-02-23 |
| EP0078191B1 (de) | 1986-09-03 |
| DE78191T1 (de) | 1983-09-15 |
| JPH0365325B2 (de) | 1991-10-11 |
| US4428939A (en) | 1984-01-31 |
| ZA827359B (en) | 1983-08-31 |
| IL67027A (en) | 1986-11-30 |
| ATE21823T1 (de) | 1986-09-15 |
| CA1239393A (en) | 1988-07-19 |
| EP0078191A3 (en) | 1983-08-17 |
| JPS58140022A (ja) | 1983-08-19 |
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